At present, treatment of type I (insulin-dependent) diabetes inevitably depends on subcutaneous insulin injection, and it is desired to develop an oral remedy for it in place of insulin. Some remedies have been developed for type II (insulin-independent) diabetes derived from stress, obesity, lack of exercise, ageing or the like, and have been tried in clinical treatment. However, none of them is a panacea and some often cause a problem of side effects. One of such remedies is vanadyl sulfate, and it has already been tried in clinical treatment in USA etc. In addition, vanadyl sulfate and bispicolinic acid/vanadyl complex are commercially available in USA as supplementary health foods.
On the other hand, it has been known that zinc(II) ion, which is known to be less toxic than vanadium, has insulin-like activity since around 1980 (L. Coulston and P. Dandona, “Insulin-like effects of Zn2+ on adipocytes”, Diabetes, 29, 665-7 (1980); J. M. May and C. S. Contoreggi, “The mechanism of the insulin-like effects of ionic zinc”, J. Biol. Chem., 257, 4362-8 (1982), and A. Shisheva, D. Gefel and Y. Shechter, “Insulin-like effects of zinc ion in vitro and in vivo” (Zn2+ is the first agent other than vanadate that on oral administration is able to restore tissue ability to metabolism glucose), Diabetes, 41, 982-8 (1992)). Since vanadyl sulfate and zinc(II) ion (zinc sulfate and zinc chloride) are inorganic salts, they are hardly permeable through bio-membranes and are therefore hardly taken into living bodies. To overcome the problems, zinc(II) complexes, which are less toxic than vanadium and are favorably stable and fat-soluble and have insulin-like activity, may be more effective than vanadyl complexes, and developing them is desired.
On the other hand, zinc that is contained in brewer's yeast and seaweed extracts is commercially available in Japan as supplementary health foods.
Regarding zinc complexes, the present inventors have already filed a patent application that has been already published, International Publication WO01/39769A1 (international publication date: Jun. 7, 2001) “Hypoglycemic Agent Comprising Zinc(II) Organic Complex”; and some reports have been announced (for example, Y. Yoshikawa, E. Ueda, Y. Suzuki, N. Yanagihara, H. Sakurai and Y. Kojima, “New Insulinomimetic Zinc(II) Complexes of α-Amino Acids and their Dervatives with Zn(N2O2) Coordination Mode”, Chem. Pharm. Bull., 49, 652-654 (2001); Yoshikawa, Ueda, Sakurai and Kojima, “Development and Study of Zinc(II) Complexes with Hypoglycemic Activity”, Biomed Res Trace Elements, 12, 104-109 (2001)). However, it is desired to further develop more effective hypoglycemic agents comprising a complex that is less toxic and has higher activity and to develop foods such as health foods and supplementary health foods having the effect.